866030-35-5

Usage

Uses

Intermediate in the preparation of Aliskiren.

Upstream product

• 172900-92-4 (1S,4S,2'S)-(4-benzyloxymethyl-2-hydroxy-1-{2'-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl}-5-methylhexyl)carbamic acid tert-butyl ester 
• 621-59-0 isovanillin 
• 365541-74-8 (4R)-3-{(2S)-3-methyl-1-oxo-2-[(phenylmethoxy)methyl]butyl}-4-(phenylmethyl)oxazolidin-2-one 
• 172901-00-7 (2S)-(benzyloxymethyl)-3-methyl-butyl bromide 
• 656241-26-8 (2S)-3-methyl-2-[(phenylmethoxy)methyl]butanoic acid 
• 934841-22-2 C₃₀H₄₇NO₈ 
• 934841-36-8 imidazole-1-carbothioic acid O-{(S)-2-[(S)-2-tert-butoxycarbonylamino-2-((2S,4S)-4-isopropyl-5-oxo-tetrahydro-furan-2-yl)-ethyl]-1-[4-methoxy-3-(3-methoxy-propoxy)-phenyl]-3-methyl-butyl} ester 
• 24424-99-5 di-tert-butyl dicarbonate 
• 173336-76-0 4-bromo-1-methoxy-2-(3-methoxypropoxy)benzene 
• 1290075-63-6 C₂₁H₂₉NO₃ 
• 1290075-65-8 C₃₂H₄₅NO₆ 
• 1297610-74-2 C₂₅H₄₁NO₅*ClH 
• 1297610-75-3 C₁₅H₁₇NO₄ 
• 1297610-73-1 C₂₁H₂₉NO₄ 

Downstream Products

• 173338-07-3 tert-butyl (3S,5S,6S,8S)-8-(3-amino-2,2-dimethyl-3-oxopropylcarbamoyl)-6-hydroxy-3-(4-methoxy-3-(3-methoxypropoxy)benzyl)-2,9-dimethyldecan-5-ylcarbamate 
• 173337-63-8 (1S,2S,4S,2'S)-(4-butylcarbamoyl-2-hydroxy-1-{2'-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl}-5-methylhexyl)carbamic acid tert-butyl ester 
• 1243342-34-8 C₃₅H₆₂N₂O₇ 
• 1243342-32-6 C₃₆H₆₄N₂O₇ 
• 1243342-36-0 C₃₆H₆₂N₂O₇ 
• 853273-53-7 ((1S,2S,4S)-4-benzylcarbamoyl-2-hydroxy-1-{(S)-2-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3-methyl-butyl}-5-methyl-hexyl)-carbamic acid tert-butyl ester 

Relevant academic research and scientific papers

Aliskiren intermediate preparation method

The present invention relates to the technical field of pharmaceutical preparation method, the preparation method of the existing long reaction time, the problem of low yield, provides a aliskiren preparation method, comprises the following steps: S1, 1st intermediate preparation: the raw material is dissolved in a solvent, adding sodium hypochlorite and sodium bisulfite reaction, shall be 1st intermediate; S2, intermediate in the preparation of 2nd: to the 1st intermediate dropping 4 - bromo - 1 - methoxy - 2 - (3 - methoxy third oxygen radical) benzene, tetrahydrofuran solution, adding low [...] catalyst, to obtain the 2nd intermediate; S3, aliskiren intermediate preparation: will be soluble in ethyl acetate in the 2nd intermediate, then adding water, nitrogen replacement 3 times, the hydrogen replaced 3 times after adding the hydrogen hydrogenation reaction, to obtain the product. By adding low deuterium water as a catalyst, help to accelerate the step S2 of the reaction rate, the reaction time is shortened, while at the same time help to improve the step S2 in the reaction yield, and then make the total reaction yield can be improved.

Convergent Synthesis of the Renin Inhibitor Aliskiren Based on C5-C6 Disconnection and CO2H-NH2 Equivalence

A novel synthesis of the renin inhibitor aliskiren based on an unprecedented disconnection between C5 and C6 was developed, in which the C5 carbon acts as a nucleophile and the amino group is introduced by a Curtius rearrangement, which follows a simultaneous stereocontrolled generation of the C4 and C5 stereogenic centers by an asymmetric hydrogenation. Operational simplicity, step economy, and a good overall yield makes this synthesis amenable to manufacture on scale.

A stereoselective catalytic nitroaldol reaction as the key step in a strategy for the synthesis of the renin inhibitor aliskiren

Aliskiren is the first-in-class orally active direct renin inhibitor. It was approved in 2007 for the treatment of hypertension. We have designed a new strategy for the convergent synthesis of aliskiren that involves a catalytic stereoselective nitroaldol reaction as the key step. A new enantiopure nitroalkane (synthon A1), prepared in only three steps from a commercially available enantiopure 2-(arylmethyl)-3-methyl butanol derivative, was successfully used in a copper-catalysed Henry reaction to give a nitrolactone intermediate in which the correct configuration for the final product was established at all four stereocentres. Nitro-group reduction, Boc-protection of the resulting amine, aminolysis of the lactone with 3-amino-2,2-dimethylpropionamide, and finally Boc-deprotection led to the enantiopure renin inhibitor aliskiren.

PROCESS FOR PREPARING 8-ARYLOCTANOIC ACIDS

The present invention relates to a process for preparing aliskiren and, more particularly, to an improved method for synthesizing a β-amino alcohol or a lactone analog thereof via the corresponding nitro derivatives of formula (Ia) or (Ib) these intermediates being used in the preparation of aliskiren.

PROCESS FOR THE PREPARATION OF ALISKIREN

The present invention provides a novel process and novel intermediates useful in the synthesis of pharmaceutically active compounds, especially renin inhibitors, such as Aliskiren, or a salt thereof, preferably Aliskiren hemifumarate.

METHOD FOR PREPARING ALISKIREN AND ITS INTERMEDIATES THEREOF

A method for preparing Aliskiren and intermediate thereof, which comprises the following steps: reacting 4-bromo-1-methoxy-2-(3-methoxypropoxy)benzene with magnesium isopropyl chloride and n-BuLi to obtain the compound of formula XXII; reacting the product of methylsulfonylation of the compound of formula XIX with anhydrous LiBr to obtain the compound of formula XXI; obtaining the intermediate of Aliskiren shown as formula XV by reacting the compound of formula XXII with the compound of formula XXI in an ether as the solvent and in the presence of a catalyst containing iron; then reacting the compound of formula XV with the compound of formula VII to obtain the compound of formula XXIII, following removing R1 from the amino group and obtaining Aliskiren shown as formula I.

PROCESS FOR THE PREPARATION OF ALISKIREN

The present invention provides a novel process and novel intermediates useful in the synthesis of pharmaceutically active compounds, especially renin inhibitors, such as Aliskiren, or a salt thereof, preferably Aliskiren hemifumarate.

Process for Producing Aliskiren

A new route of synthesis of the compound Aliskiren of formula (I), used in the treatment of hypertension, is described.

METHOD FOR PREPARING ALISKIREN AND INTERMEDIATE THEREOF

A method for preparing Aliskiren and intermediate thereof, which comprises the following steps: reacting 4-bromo-1-methoxy-2-(3-methoxypropoxy)benzene with magnesium isopropyl chloride and n-BuLi to obtain the compound of formula XXII; reacting the product of methylsulfonylation of the compound of formula XIX with anhydrous LiBr to obtain the compound of formula XXI; obtaining the intermediate of Aliskiren shown as formula XV by reacting the compound of formula XXII with the compound of formula XXI in an ether as the solvent and in the presence of a catalyst containing iron; then reacting the compound of formula XV with the compound of formula VII to obtain the compound of formula XXIII, following removing R1 from the amino group and obtaining Aliskiren shown as formula I.

Manufacturing process for 8-aryloctanoic acids such as Aliskiren

The present invention relates to a novel manufacturing process and novel intermediates useful in the synthesis of pharmaceutically active compound such as Aliskiren. The invention describes preparation of enantiomerically pure 8-aryloctanoic acid of formu